Ortho-Clinical Diagnostics Receives PMA Approval for First Hepatitis Assay as an Aid in Determining Immunity to Hepatitis B Virus Using a Random Access System

Apr 02, 2001, 01:00 ET from Ortho-Clinical Diagnostics

    RARITAN, N.J., April 2 /PRNewswire/ -- The first diagnostic anti-hepatitis
 B surface antigen assay on a random access system has received Premarket
 Approval (PMA) by the U.S. Food and Drug Administration's Center for Devices
 and Radiological Health.  Developed by Ortho-Clinical Diagnostics, Inc. (OCD),
 this assay can be used as an aid in determining immunity of an individual to
 hepatitis B virus (HBV).
     The VITROS(R) Immunodiagnostic Products Anti-HBs Reagent Pack and
 Calibrators (VITROS Anti-HBs assay) is for the qualitative in vitro
 determination of total antibody to hepatitis B surface antigen (anti-HBs) in
 human serum using the VITROS ECi Immunodiagnostic System.
     Assay results may be used as an aid in the determination of susceptibility
 to hepatitis B virus (HBV) infection for individuals prior to or following HBV
 vaccination, or where vaccination status is unknown.  Assay results may be
 used with other HBV serological markers for the laboratory diagnosis of HBV
 disease associated with HBV infection.  A reactive assay result will allow a
 differential diagnosis in individuals displaying signs and symptoms of
 hepatitis, in whom etiology is unknown.(1)
     A positive assay result is consistent with levels of anti-HBs greater than
 or equal to 10mIU/mL.  The accepted criterion for immunity to HBV is greater
 than or equal to 10mIU/mL of anti-HBs, with mIU/mL defined by the World Health
 Organization (WHO) Reference Preparation.(2,3,4)  Calibration of the VITROS
 Anti-HBs assay is traceable to the WHO First International Reference
 Preparation for Antibody to HBsAg (1977).
     The VITROS ECi Immunodiagnostic System (VITROS ECi System) is fully
 automated, random access and uses enhanced chemiluminescence technology to
 provide high sensitivity, precision and dynamic range.  The VITROS ECi System
 offers walk-away convenience for routine immunoassays, and permits tests to be
 run at any time in any order. And the VITROS ECi System also has a new
 enhancement, called Intellicheck(TM), for monitoring sample, process and
 result integrity.
     "With the goal of providing our customers with new methods to expand their
 testing capabilities and deliver results sooner to physicians and ultimately
 their patients, Ortho-Clinical Diagnostics is extending its competency in
 hepatitis testing and random access testing on the VITROS ECi Immunodiagnostic
 System," said Catherine Burzik, President, Americas, Ortho-Clinical
 Diagnostics.  "This new diagnostic hepatitis assay is the first in a series we
 anticipate marketing for the VITROS ECi Immunodiagnostic System."
     "The prospective clinical study that evaluated the assay included
 individuals with signs and symptoms of hepatitis and persons recognized to be
 at risk for HBV infection due to occupation, lifestyle, behavior, or known
 exposure events, as well as retrospective samples from individuals with a
 known vaccination history," explained David Ciavarella, M.D., Executive
 Director, Medical Affairs, OCD.
     "Results from the VITROS Anti-HBs assay can aid physicians in advising
 patients if sufficient antibodies are present for protective immunity to HBV.
 This information is particularly important for high-risk individuals, such as
 health care workers.  A recent study(5) conducted among health care workers
 reported that twenty-nine percent of the health care workers who were
 vaccinated against hepatitis B showed no serologic evidence of immunity four
 to five years post vaccination," said Dr. Ciavarella.
     The VITROS Anti-HBs assay also supports the post-vaccination guidelines
 set forth by the Centers for Disease Control and Prevention as they pertain to
 immunity testing among those whose "clinical management depends on knowledge
 of their immune status" (and) "who through occupational risk may be exposed to
 injuries with sharp instruments.  Knowledge of their antibody response will
 help determine appropriate post-exposure prophylaxis".(6)
     Approval of OCD's VITROS Anti-HBs assay expands the menu of the random
 access tests available on the VITROS ECi Immunodiagnostic System and extends
 OCD's competency in the clinical laboratory to include infectious disease (ID)
 diagnostic testing.  The VITROS Anti-HBs assay, first introduced outside the
 United States in 1998, has provided millions of results to guide physicians on
 the care of their patients.
     "This assay offers significant efficiencies for the clinical laboratory,"
 states Michael DeLucia, Product Director for Infectious Diseases, OCD. "Batch
 testing can be eliminated, results can be provided in about 55 minutes, and
 reagent packs are stable for up to eight weeks on board the VITROS ECi System.
 This assay will dramatically change the clinical laboratory's ability to serve
 their customers."
     With the addition of the Anti-HBs assay, the VITROS ECi menu now includes
 more than 25 current analytes for thyroid function, reproductive health and
 fertility, bone metabolism, anemia, metabolic, emergency cardiology, and
 oncology markers already available.
     Ortho-Clinical Diagnostics, a Johnson & Johnson Company, is a leading
 provider of high-value diagnostic solutions for the global health care
 community.  Committed to developing the most advanced tests for early
 detection or diagnosis of disease, the Company brings products to market that
 provide timely information and help to facilitate better medical decisions.
 Ortho-Clinical Diagnostics also provides blood screening and typing products
 that help to ensure the safety of the world's blood supply.  In addition,
 through its patented dry slide and enhanced chemiluminescence technologies,
 the Company transformed the way that clinical laboratories perform testing.
 Worldwide, health care professionals rely on Ortho-Clinical Diagnostics for
 innovative diagnostic solutions that promote effective diagnoses and enhanced
 patient care.
 
      (1) VITROS Immunodiagnostic Products Anti-HBs Reagent Pack Methodology
          Sheet.  Refer to appropriate sections for additional information
          related to warnings and precautions about this device.
 
      (2) Hepatitis B Virus: A Comprehensive Strategy for Eliminating
          Transmission in the United States Through Universal Childhood
          Vaccination: Recommendations of the Immunization Practices Advisory
          Committee (ACIP). MMWR 1991; 40 (RR-13):8.
 
      (3) Hollinger FB. In Fields B, Knipe DM, Howley PM (eds).  Fields
          Virology.  Philadelphia: Lippincott-Raven Publishers, 1996:2739-2807.
 
      (4) Recommendations of the Immunization Practices Advisory Committee
          Update on Hepatitis B Prevention. MMWR 1987; 36(23):353-366.
 
      (5) Barash C, Conn MI, DiMarino AJ, Marzano J, Allen ML. Serologic
          Hepatitis B Immunity in Vaccinated Health Care Workers.  Archives of
          Internal Medicine 1999;159:1481-1483.
 
      (6) National Center for Infectious Disease, Viral Hepatitis B. "Hepatitis
          B Virus: A Comprehensive Strategy for Eliminating Transmission in the
          United States Through Universal Childhood Vaccination:
          Recommendations of the Immunization Practices Advisory Committee
          (ACIP). MMWR 1991; 40 (RR-13):1-19, Publication date, 11/22/1991.
 
 
 
              VITROS(R) Immunodiagnostic Products Anti-HBs Reagent
                              Pack and Calibrators
                            (VITROS Anti-HBs Assay)
                                     Q & A
 
     What is hepatitis B?
     Hepatitis B is an inflammation of the liver due to the presence of the
 hepatitis B virus or HBV.  The virus is transmitted via the blood, sexually or
 perinatally and presents with the following clinical features: jaundice,
 fatigue, abdominal pain, loss of appetite, intermittent nausea, and vomiting.
     The Centers for Disease Control and Prevention (CDC) estimates that there
 are 140,000-320,000 infections/year and that about 50 percent are
 asymptomatic.  Additionally, 1-1.25 million Americans are estimated to be
 chronically infected.(1)
     The number of cases peaked in 1985, but have since dramatically decreased
 by 55 percent through 1993 because of the wider use of vaccine among adults,
 modification in high-risk practices and more universal vaccination of newborns
 and 11-12 year olds in more recent years.
 
     Who is at risk for hepatitis B?
     According to the Centers for Disease Control and Prevention (CDC), high-
 risk groups include, but are not limited to, health care workers,
 repeated/household/sexual contacts of infected persons, hemodialysis patients,
 intravenous drug users, sexually active heterosexuals with multiple partners,
 men who have sex with men, infants born to infected mothers and
 infants/children of immigrants from disease-endemic areas.(1)
 
     How can you test for susceptibility and/or immunity to hepatitis B?
     Following HBV vaccination as well as after resolution of an HBV infection,
 a physician can request to have a blood sample taken and tested for antibody
 to hepatitis B surface antigen.  The accepted criterion for immunity to HBV is
 greater than or equal to 10mIU/mL of anti-HBs.
     The VITROS Immunodiagnostic Products Anti-HBs Reagent Pack and Calibrators
 (VITROS Anti-HBs assay) is for the qualitative in vitro determination of total
 antibody to hepatitis B surface antigen (anti-HBs) in human serum using the
 VITROS ECi Immunodiagnostic System.
     Assay results may be used as an aid in the determination of susceptibility
 to hepatitis B virus (HBV) infection for individuals prior to or following HBV
 vaccination, or where vaccination status is unknown.  Assay results may be
 used with other HBV serological markers for the laboratory diagnosis of HBV
 disease associated with HBV infection.  A reactive assay result will allow a
 differential diagnosis in individuals displaying signs and symptoms of
 hepatitis, in whom etiology is unknown.(2)
     The VITROS Anti-HBs assay results are based on a cutoff established with
 calibrators traceable to the WHO First International Reference Preparation for
 Antibody to HBsAg (1977).  A value of 10mIU/mL was normalized to a VITROS
 Anti-HBs assay result of 1.00.(2)  Individuals whose results are positive by
 the VITROS Anti-HBs assay can be considered to have anti-HBs levels consistent
 with protective immunity against HBV infection.(3,4,5)
 
     What is the VITROS Anti-HBs assay?
     The VITROS Anti-HBs assay is the first diagnostic anti-hepatitis B surface
 antigen assay to be approved by the Food and Drug Administration's Center for
 Devices and Radiological Health.  In order to support the utility of the
 assay, Ortho-Clinical Diagnostics conducted a multi-center clinical study with
 samples collected from centers across the nation.  The study was designed to
 evaluate prospectively collected specimens from individuals with signs and
 symptoms of hepatitis and individuals recognized to be at risk for HBV
 infection due to occupation, lifestyle, behavior, or known exposure events.
 The study also utilized retrospective samples from individuals with a well-
 documented history of vaccination to HBV.
 
     How is the test performed?
     The VITROS Anti-HBs assay is performed using the VITROS ECi
 Immunodiagnostic System.  This fully automated, random access immunoassay
 analyzer uses enhanced chemiluminescence technology to provide superior
 sensitivity, precision and dynamic range.  The VITROS ECi System offers walk-
 away convenience for routine immunoassays, and now for infectious disease
 tests which can be run at any time in any order.
 
     How are the test results reported?
     Using the VITROS Anti-HBs assay, results are reported as negative
 (antibody level detected is not sufficient for immunity) or positive (antibody
 detected at levels consistent with immunity).  Indeterminate results can also
 be reported indicating additional follow-up by a physician may be required.
 VITROS Anti-HBs assay results can aid physicians in advising patients if
 sufficient antibodies are present for protective immunity to HBV. This
 information is particularly important for high-risk individuals, such as
 health care workers and hemodialysis patients.
 
     Is there evidence to suggest that individuals vaccinated against hepatitis
 B may not retain antibody levels?
     There is a recent study(6) authored by Anthony DiMarino, Jr., MD et al. of
 Thomas Jefferson University, Philadelphia, PA, that assessed the hepatitis B
 serologic immune status of health care workers who were previously vaccinated.
 
     Conclusion of the study: Twenty-nine percent of the health care workers
 who were vaccinated against hepatitis B showed no serologic evidence of
 hepatitis B immunity four to five years post vaccination.  It is unclear
 whether these subjects were non-responders, lost immunity or retained
 anamnestic potential.
 
     Recommendations of the study:
     -- Post-vaccination testing within one to two months to document immunity
     -- Periodic anti-HBs monitoring
     -- Booster vaccination to maintain protective titer levels
     Note that full text of study is available upon request.
 
     How is the VITROS Anti-HBs assay different from other assays for anti-HBs?
     The VITROS Anti-HBs assay is different in many ways.  It is the first
 anti-HBs assay to be approved by the FDA, Center for Devices and Radiological
 Health (CDRH), with diagnostic indications for use as an aid in the
 determination of susceptibility to HBV infection for individuals prior to or
 following HBV vaccination, or where vaccination status is unknown. Clinical
 performance data are provided in the product labeling to support this claim.
 Most results reported today in the clinical laboratory use qualitative assays
 for the determination of the presence of anti-HBs and no further claims are
 made.  The cutoff is established using negative controls (no anti-HBs). A
 positive result means that antibody is present.  These tests are only
 indicative of a prior immunologic exposure to the antigen or vaccine and
 immune status cannot be determined.
     A "positive" result with the VITROS Anti-HBs assay is interpreted as
 having a level of antibody to hepatitis B surface antigen greater than or
 equal to 10mIU/mL and consistent with protective immunity.  An "indeterminate"
 result in the VITROS Anti-HBs assay indicates that the individual should be
 further assessed by considering other factors, such as clinical status,
 follow-up testing, associated risk factors, and the use of additional
 diagnostic information. A "negative" result with the VITROS Anti-HBs assay
 indicates that the antibody level detected is not sufficient for immunity.(2)
     Additionally, the VITROS Anti-HBs assay on the VITROS ECi Immunodiagnostic
 System can be run in random access with full walk-away capability and results
 in less than one hour. This is compared to current methods that require
 multiple manual steps, multiple incubation steps and a minimal time to result
 of approximately five hours.
     The VITROS Anti-HBs assay was evaluated using samples prospectively
 collected from individuals with signs and symptoms of hepatitis as well as
 retrospective samples from individuals with a well-documented vaccination
 history.  The samples were then characterized as to their clinical status
 using multiple hepatitis markers.  The study design describes testing of the
 same populations in trials for which the test is indicated in clinical use.
 It may serve as a standard as to how diagnostic assays for hepatitis will be
 evaluated in the future.
 
     How has Ortho-Clinical Diagnostics led the way in assisting to determine
 susceptibility to HBV?
     Ortho-Clinical Diagnostics can boast a number of "firsts" in the area of
 HBV immunity.  They include:
     -- First hepatitis assay for the VITROS ECi Immunodiagnostic System.
     -- First diagnostic anti-HBs assay approved by the FDA's Center for
         Devices and Radiological Health (CDRH).
     -- First hepatitis assay approved on a routine, random access immunoassay
         analyzer.
     -- First anti-HBs assay approved to aid in the determination of
         susceptibility to hepatitis B virus (HBV) infection for individuals
         prior to or following HBV vaccination or when vaccination status is
         unknown.
     -- First FDA-approved hepatitis assay utilizing chemiluminescence
         technology.
 
      (1) http://www.cdc.gov/ncidod/diseases/hepatitis/b/fact.htm
 
      (2) VITROS Immunodiagnostic Products Anti-HBs Reagent Pack Methodology
          Sheet.  Refer to appropriate sections for additional information
          related to warnings and precautions about this device.
 
      (3) Hepatitis B Virus: A Comprehensive Strategy for Eliminating
          Transmission in the United States Through Universal Childhood
          Vaccination: Recommendations of the Immunization Practices Advisory
          Committee (ACIP). MMWR 1991; 40 (RR-13):8.
 
      (4) Hollinger FB. In Fields B, Knipe DM, Howley PM (eds).  Fields
          Virology.  Philadelphia: Lippincott-Raven Publishers, 1996:2739-
          2807.
 
      (5) Recommendations of the Immunization Practices Advisory Committee
          Update on Hepatitis B Prevention. MMWR 1987; 36(23):353-366.
 
      (6) Barash C, Conn MI, DiMarino AJ, Marzano J, Allen ML. Serologic
          Hepatitis B Immunity in Vaccinated Health Care Workers.  Archives of
          Internal Medicine 1999;159:1481-1483.
 
 

SOURCE Ortho-Clinical Diagnostics
    RARITAN, N.J., April 2 /PRNewswire/ -- The first diagnostic anti-hepatitis
 B surface antigen assay on a random access system has received Premarket
 Approval (PMA) by the U.S. Food and Drug Administration's Center for Devices
 and Radiological Health.  Developed by Ortho-Clinical Diagnostics, Inc. (OCD),
 this assay can be used as an aid in determining immunity of an individual to
 hepatitis B virus (HBV).
     The VITROS(R) Immunodiagnostic Products Anti-HBs Reagent Pack and
 Calibrators (VITROS Anti-HBs assay) is for the qualitative in vitro
 determination of total antibody to hepatitis B surface antigen (anti-HBs) in
 human serum using the VITROS ECi Immunodiagnostic System.
     Assay results may be used as an aid in the determination of susceptibility
 to hepatitis B virus (HBV) infection for individuals prior to or following HBV
 vaccination, or where vaccination status is unknown.  Assay results may be
 used with other HBV serological markers for the laboratory diagnosis of HBV
 disease associated with HBV infection.  A reactive assay result will allow a
 differential diagnosis in individuals displaying signs and symptoms of
 hepatitis, in whom etiology is unknown.(1)
     A positive assay result is consistent with levels of anti-HBs greater than
 or equal to 10mIU/mL.  The accepted criterion for immunity to HBV is greater
 than or equal to 10mIU/mL of anti-HBs, with mIU/mL defined by the World Health
 Organization (WHO) Reference Preparation.(2,3,4)  Calibration of the VITROS
 Anti-HBs assay is traceable to the WHO First International Reference
 Preparation for Antibody to HBsAg (1977).
     The VITROS ECi Immunodiagnostic System (VITROS ECi System) is fully
 automated, random access and uses enhanced chemiluminescence technology to
 provide high sensitivity, precision and dynamic range.  The VITROS ECi System
 offers walk-away convenience for routine immunoassays, and permits tests to be
 run at any time in any order. And the VITROS ECi System also has a new
 enhancement, called Intellicheck(TM), for monitoring sample, process and
 result integrity.
     "With the goal of providing our customers with new methods to expand their
 testing capabilities and deliver results sooner to physicians and ultimately
 their patients, Ortho-Clinical Diagnostics is extending its competency in
 hepatitis testing and random access testing on the VITROS ECi Immunodiagnostic
 System," said Catherine Burzik, President, Americas, Ortho-Clinical
 Diagnostics.  "This new diagnostic hepatitis assay is the first in a series we
 anticipate marketing for the VITROS ECi Immunodiagnostic System."
     "The prospective clinical study that evaluated the assay included
 individuals with signs and symptoms of hepatitis and persons recognized to be
 at risk for HBV infection due to occupation, lifestyle, behavior, or known
 exposure events, as well as retrospective samples from individuals with a
 known vaccination history," explained David Ciavarella, M.D., Executive
 Director, Medical Affairs, OCD.
     "Results from the VITROS Anti-HBs assay can aid physicians in advising
 patients if sufficient antibodies are present for protective immunity to HBV.
 This information is particularly important for high-risk individuals, such as
 health care workers.  A recent study(5) conducted among health care workers
 reported that twenty-nine percent of the health care workers who were
 vaccinated against hepatitis B showed no serologic evidence of immunity four
 to five years post vaccination," said Dr. Ciavarella.
     The VITROS Anti-HBs assay also supports the post-vaccination guidelines
 set forth by the Centers for Disease Control and Prevention as they pertain to
 immunity testing among those whose "clinical management depends on knowledge
 of their immune status" (and) "who through occupational risk may be exposed to
 injuries with sharp instruments.  Knowledge of their antibody response will
 help determine appropriate post-exposure prophylaxis".(6)
     Approval of OCD's VITROS Anti-HBs assay expands the menu of the random
 access tests available on the VITROS ECi Immunodiagnostic System and extends
 OCD's competency in the clinical laboratory to include infectious disease (ID)
 diagnostic testing.  The VITROS Anti-HBs assay, first introduced outside the
 United States in 1998, has provided millions of results to guide physicians on
 the care of their patients.
     "This assay offers significant efficiencies for the clinical laboratory,"
 states Michael DeLucia, Product Director for Infectious Diseases, OCD. "Batch
 testing can be eliminated, results can be provided in about 55 minutes, and
 reagent packs are stable for up to eight weeks on board the VITROS ECi System.
 This assay will dramatically change the clinical laboratory's ability to serve
 their customers."
     With the addition of the Anti-HBs assay, the VITROS ECi menu now includes
 more than 25 current analytes for thyroid function, reproductive health and
 fertility, bone metabolism, anemia, metabolic, emergency cardiology, and
 oncology markers already available.
     Ortho-Clinical Diagnostics, a Johnson & Johnson Company, is a leading
 provider of high-value diagnostic solutions for the global health care
 community.  Committed to developing the most advanced tests for early
 detection or diagnosis of disease, the Company brings products to market that
 provide timely information and help to facilitate better medical decisions.
 Ortho-Clinical Diagnostics also provides blood screening and typing products
 that help to ensure the safety of the world's blood supply.  In addition,
 through its patented dry slide and enhanced chemiluminescence technologies,
 the Company transformed the way that clinical laboratories perform testing.
 Worldwide, health care professionals rely on Ortho-Clinical Diagnostics for
 innovative diagnostic solutions that promote effective diagnoses and enhanced
 patient care.
 
      (1) VITROS Immunodiagnostic Products Anti-HBs Reagent Pack Methodology
          Sheet.  Refer to appropriate sections for additional information
          related to warnings and precautions about this device.
 
      (2) Hepatitis B Virus: A Comprehensive Strategy for Eliminating
          Transmission in the United States Through Universal Childhood
          Vaccination: Recommendations of the Immunization Practices Advisory
          Committee (ACIP). MMWR 1991; 40 (RR-13):8.
 
      (3) Hollinger FB. In Fields B, Knipe DM, Howley PM (eds).  Fields
          Virology.  Philadelphia: Lippincott-Raven Publishers, 1996:2739-2807.
 
      (4) Recommendations of the Immunization Practices Advisory Committee
          Update on Hepatitis B Prevention. MMWR 1987; 36(23):353-366.
 
      (5) Barash C, Conn MI, DiMarino AJ, Marzano J, Allen ML. Serologic
          Hepatitis B Immunity in Vaccinated Health Care Workers.  Archives of
          Internal Medicine 1999;159:1481-1483.
 
      (6) National Center for Infectious Disease, Viral Hepatitis B. "Hepatitis
          B Virus: A Comprehensive Strategy for Eliminating Transmission in the
          United States Through Universal Childhood Vaccination:
          Recommendations of the Immunization Practices Advisory Committee
          (ACIP). MMWR 1991; 40 (RR-13):1-19, Publication date, 11/22/1991.
 
 
 
              VITROS(R) Immunodiagnostic Products Anti-HBs Reagent
                              Pack and Calibrators
                            (VITROS Anti-HBs Assay)
                                     Q & A
 
     What is hepatitis B?
     Hepatitis B is an inflammation of the liver due to the presence of the
 hepatitis B virus or HBV.  The virus is transmitted via the blood, sexually or
 perinatally and presents with the following clinical features: jaundice,
 fatigue, abdominal pain, loss of appetite, intermittent nausea, and vomiting.
     The Centers for Disease Control and Prevention (CDC) estimates that there
 are 140,000-320,000 infections/year and that about 50 percent are
 asymptomatic.  Additionally, 1-1.25 million Americans are estimated to be
 chronically infected.(1)
     The number of cases peaked in 1985, but have since dramatically decreased
 by 55 percent through 1993 because of the wider use of vaccine among adults,
 modification in high-risk practices and more universal vaccination of newborns
 and 11-12 year olds in more recent years.
 
     Who is at risk for hepatitis B?
     According to the Centers for Disease Control and Prevention (CDC), high-
 risk groups include, but are not limited to, health care workers,
 repeated/household/sexual contacts of infected persons, hemodialysis patients,
 intravenous drug users, sexually active heterosexuals with multiple partners,
 men who have sex with men, infants born to infected mothers and
 infants/children of immigrants from disease-endemic areas.(1)
 
     How can you test for susceptibility and/or immunity to hepatitis B?
     Following HBV vaccination as well as after resolution of an HBV infection,
 a physician can request to have a blood sample taken and tested for antibody
 to hepatitis B surface antigen.  The accepted criterion for immunity to HBV is
 greater than or equal to 10mIU/mL of anti-HBs.
     The VITROS Immunodiagnostic Products Anti-HBs Reagent Pack and Calibrators
 (VITROS Anti-HBs assay) is for the qualitative in vitro determination of total
 antibody to hepatitis B surface antigen (anti-HBs) in human serum using the
 VITROS ECi Immunodiagnostic System.
     Assay results may be used as an aid in the determination of susceptibility
 to hepatitis B virus (HBV) infection for individuals prior to or following HBV
 vaccination, or where vaccination status is unknown.  Assay results may be
 used with other HBV serological markers for the laboratory diagnosis of HBV
 disease associated with HBV infection.  A reactive assay result will allow a
 differential diagnosis in individuals displaying signs and symptoms of
 hepatitis, in whom etiology is unknown.(2)
     The VITROS Anti-HBs assay results are based on a cutoff established with
 calibrators traceable to the WHO First International Reference Preparation for
 Antibody to HBsAg (1977).  A value of 10mIU/mL was normalized to a VITROS
 Anti-HBs assay result of 1.00.(2)  Individuals whose results are positive by
 the VITROS Anti-HBs assay can be considered to have anti-HBs levels consistent
 with protective immunity against HBV infection.(3,4,5)
 
     What is the VITROS Anti-HBs assay?
     The VITROS Anti-HBs assay is the first diagnostic anti-hepatitis B surface
 antigen assay to be approved by the Food and Drug Administration's Center for
 Devices and Radiological Health.  In order to support the utility of the
 assay, Ortho-Clinical Diagnostics conducted a multi-center clinical study with
 samples collected from centers across the nation.  The study was designed to
 evaluate prospectively collected specimens from individuals with signs and
 symptoms of hepatitis and individuals recognized to be at risk for HBV
 infection due to occupation, lifestyle, behavior, or known exposure events.
 The study also utilized retrospective samples from individuals with a well-
 documented history of vaccination to HBV.
 
     How is the test performed?
     The VITROS Anti-HBs assay is performed using the VITROS ECi
 Immunodiagnostic System.  This fully automated, random access immunoassay
 analyzer uses enhanced chemiluminescence technology to provide superior
 sensitivity, precision and dynamic range.  The VITROS ECi System offers walk-
 away convenience for routine immunoassays, and now for infectious disease
 tests which can be run at any time in any order.
 
     How are the test results reported?
     Using the VITROS Anti-HBs assay, results are reported as negative
 (antibody level detected is not sufficient for immunity) or positive (antibody
 detected at levels consistent with immunity).  Indeterminate results can also
 be reported indicating additional follow-up by a physician may be required.
 VITROS Anti-HBs assay results can aid physicians in advising patients if
 sufficient antibodies are present for protective immunity to HBV. This
 information is particularly important for high-risk individuals, such as
 health care workers and hemodialysis patients.
 
     Is there evidence to suggest that individuals vaccinated against hepatitis
 B may not retain antibody levels?
     There is a recent study(6) authored by Anthony DiMarino, Jr., MD et al. of
 Thomas Jefferson University, Philadelphia, PA, that assessed the hepatitis B
 serologic immune status of health care workers who were previously vaccinated.
 
     Conclusion of the study: Twenty-nine percent of the health care workers
 who were vaccinated against hepatitis B showed no serologic evidence of
 hepatitis B immunity four to five years post vaccination.  It is unclear
 whether these subjects were non-responders, lost immunity or retained
 anamnestic potential.
 
     Recommendations of the study:
     -- Post-vaccination testing within one to two months to document immunity
     -- Periodic anti-HBs monitoring
     -- Booster vaccination to maintain protective titer levels
     Note that full text of study is available upon request.
 
     How is the VITROS Anti-HBs assay different from other assays for anti-HBs?
     The VITROS Anti-HBs assay is different in many ways.  It is the first
 anti-HBs assay to be approved by the FDA, Center for Devices and Radiological
 Health (CDRH), with diagnostic indications for use as an aid in the
 determination of susceptibility to HBV infection for individuals prior to or
 following HBV vaccination, or where vaccination status is unknown. Clinical
 performance data are provided in the product labeling to support this claim.
 Most results reported today in the clinical laboratory use qualitative assays
 for the determination of the presence of anti-HBs and no further claims are
 made.  The cutoff is established using negative controls (no anti-HBs). A
 positive result means that antibody is present.  These tests are only
 indicative of a prior immunologic exposure to the antigen or vaccine and
 immune status cannot be determined.
     A "positive" result with the VITROS Anti-HBs assay is interpreted as
 having a level of antibody to hepatitis B surface antigen greater than or
 equal to 10mIU/mL and consistent with protective immunity.  An "indeterminate"
 result in the VITROS Anti-HBs assay indicates that the individual should be
 further assessed by considering other factors, such as clinical status,
 follow-up testing, associated risk factors, and the use of additional
 diagnostic information. A "negative" result with the VITROS Anti-HBs assay
 indicates that the antibody level detected is not sufficient for immunity.(2)
     Additionally, the VITROS Anti-HBs assay on the VITROS ECi Immunodiagnostic
 System can be run in random access with full walk-away capability and results
 in less than one hour. This is compared to current methods that require
 multiple manual steps, multiple incubation steps and a minimal time to result
 of approximately five hours.
     The VITROS Anti-HBs assay was evaluated using samples prospectively
 collected from individuals with signs and symptoms of hepatitis as well as
 retrospective samples from individuals with a well-documented vaccination
 history.  The samples were then characterized as to their clinical status
 using multiple hepatitis markers.  The study design describes testing of the
 same populations in trials for which the test is indicated in clinical use.
 It may serve as a standard as to how diagnostic assays for hepatitis will be
 evaluated in the future.
 
     How has Ortho-Clinical Diagnostics led the way in assisting to determine
 susceptibility to HBV?
     Ortho-Clinical Diagnostics can boast a number of "firsts" in the area of
 HBV immunity.  They include:
     -- First hepatitis assay for the VITROS ECi Immunodiagnostic System.
     -- First diagnostic anti-HBs assay approved by the FDA's Center for
         Devices and Radiological Health (CDRH).
     -- First hepatitis assay approved on a routine, random access immunoassay
         analyzer.
     -- First anti-HBs assay approved to aid in the determination of
         susceptibility to hepatitis B virus (HBV) infection for individuals
         prior to or following HBV vaccination or when vaccination status is
         unknown.
     -- First FDA-approved hepatitis assay utilizing chemiluminescence
         technology.
 
      (1) http://www.cdc.gov/ncidod/diseases/hepatitis/b/fact.htm
 
      (2) VITROS Immunodiagnostic Products Anti-HBs Reagent Pack Methodology
          Sheet.  Refer to appropriate sections for additional information
          related to warnings and precautions about this device.
 
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 SOURCE  Ortho-Clinical Diagnostics